Download PDF
Synlett 2006(18): 3164-3166  
DOI: 10.1055/s-2006-941600
LETTER
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Synthesis of trans-2-Substituted Cyclopropylamines [1]

Chloé Tanguya,b, Philippe Bertusa, Jan Szymoniak*a, Oleg V. Larionovb, Armin de Meijere*b
a Réactions Sélectives et Applications, CNRS (UMR6519) and Université de Reims, 51687 Reims Cedex 2, France
Fax: +33(3)26913166; e-Mail: jan.szymoniak@univ-reims.fr;
b Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
Fax: +49(551)399475; e-Mail: Armin.deMeijere@chemie.uni-goettingen.de;
Further Information

Publication History

Received 28 March 2006
Publication Date:
29 June 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

Upon treatment with n-butyllithium at -30 °C, the ­readily available trans-2-(tributylstannyl)-N,N-dibenzylcyclo­propylamine undergoes tin-lithium exchange with retention of configuration, and trapping of the resulting aminocyclopropyllithium species with a range of electrophiles including alkyl and allyl ­bromides or iodides, disulfides, aldehydes and imines, affords the title compounds in moderate to good yields (69-89%).

Key words

cyclopropylamines - titanium - trans-stereoselectivity - tin-lithium exchange

    References and Notes

  • For one of us (AdM) this is to count as Part 127 in the series ‘Cyclopropyl Building Blocks for Organic Synthesis’. For Part 126, see:
  • 1a Larionov OV. de Meijere A. Adv. Synth. Catal.  2006,  in press 
    Article in Thieme ConnectGoogle Scholar
  • Part 125, see:
  • 1b Marradi M. Brandi A. de Meijere A. Synlett  2006,  1125 
    Article in Thieme ConnectGoogle Scholar
  • 2a Wessjohann LA. Brandt W. Thiemann T. Chem. Rev.  2003,  103:  1625 
    CrossrefGoogle Scholar
  • 2b Salaün J. Top. Curr. Chem.  2000,  207:  1 
    CrossrefGoogle Scholar
  • 2c Suckling CJ. Angew. Chem., Int. Ed. Engl.  1988,  27:  537 
    CrossrefGoogle Scholar
  • 2d Vilsmaier E. In The Chemistry of the Cyclopropyl Group   Rappoport Z. Wiley; New York: 1987.  p.1341 
    CrossrefGoogle Scholar
  • 3 Carbocyclic Three- and Four-Membered Ring Compounds, In Methods of Organic Chemistry (Houben-Weyl)   Vol. E17a-f:  de Meijere A. Thieme; Stuttgart: 1997. 
    Google Scholar
  • Reviews:
  • 4a de Meijere A. Kozhushkov SI. Savchenko AI. J. Organomet. Chem.  2004,  689:  2033 
    Google Scholar
  • 4b de Meijere A. Kozhushkov SI. Savchenko AI. Titanium and Zirconium in Organic Synthesis   Marek I. Wiley-VCH; Weinheim: 2002.  p.390 
    Google Scholar
  • 4c Kulinkovich OG. de Meijere A. Chem. Rev.  2000,  100:  2789 
    Google Scholar
  • 5a Bertus P. Szymoniak J. Chem. Commun.  2001,  1792 
    CrossrefGoogle Scholar
  • 5b Bertus P. Szymoniak J. J. Org. Chem.  2002,  67:  3965 
    CrossrefGoogle Scholar
  • 5c Bertus P. Szymoniak J. Synlett  2003,  265 
    CrossrefGoogle Scholar
  • 5d Laroche C. Bertus P. Szymoniak J. Tetrahedron Lett.  2003,  44:  2485 
    CrossrefGoogle Scholar
  • 5e Bertus P. Szymoniak J. J. Org. Chem.  2003,  68:  7133 
    CrossrefGoogle Scholar
  • 5f Laroche C. Harakat D. Bertus P. Szymoniak J. Org. Biomol. Chem.  2005,  3:  3482 
    CrossrefGoogle Scholar
  • 5g Laroche C. Behr JB. Szymoniak J. Bertus P. Plantier-Royon R. Eur. J. Org. Chem.  2005,  5084 
    CrossrefGoogle Scholar
  • 6a Lee K. Kim S.-I. Cha JK. J. Org. Chem.  1998,  63:  9135 
    CrossrefGoogle Scholar
  • 6b de Meijere A. Williams CM. Kourdioukov A. Sviridov SV. Chaplinski V. Kordes M. Savchenko AI. Stratmann C. Noltemeyer M. Chem. Eur. J.  2002,  8:  3789 
    CrossrefGoogle Scholar
  • 7 Wiedemann S. Rauch K. Savchenko A. Marek I. de Meijere A. Eur. J. Org. Chem.  2004,  631 
    CrossrefGoogle Scholar
  • 8a Seyferth D. Cohen HM. J. Organomet. Chem.  1963,  1:  15 
    CrossrefGoogle Scholar
  • 8b Tanaka K. Minami K. Funaki I. Suzuki H. Tetrahedron Lett.  1990,  31:  2727 
    CrossrefGoogle Scholar
  • 8c Isono N. Mori M. J. Org. Chem.  1996,  61:  7867 
    CrossrefGoogle Scholar
  • 8d For a review on cyclopropylstannanes, see: Rubina M. Gevorgyan V. Tetrahedron  2004,  60:  3129 
    CrossrefGoogle Scholar
  • For reviews, see:
  • 9a de Meijere A. Angew. Chem., Int. Ed. Engl.  1979,  18:  809 ; Angew. Chem. 1979, 91, 867
    Google Scholar
  • 9b Wiberg KB. Carbocyclic Three-Membered Ring Compounds, In Methods of Organic Chemistry (Houben-Weyl)   Vol. 17a:  de Meijere A. Thieme; Stuttgart: 1996. 
    Google Scholar
  • 12 The trans configuration was attributed on the basis of the J H 1 H 2 coupling constants, in accordance with the literature data, see: Vilsmaier E. The Chemistry of the Cyclopropyl Group   Part 1:  Rappoport Z. Wiley; New York: 1987.  Chap. 3. p.119 
    Google Scholar
  • 13 Brandl M. Kozhushkov SI. Loscha K. Kokoreva OV. Yufit DS. Howard JAK. de Meijere A. Synlett  2000,  1741 
    Article in Thieme ConnectGoogle Scholar
  • 14 ACC is the naturally occurring precursor of ethylene, a phytohormone responsible for fruit ripening and other plant physiological processes. Confer: Pirrung MC. Acc. Chem. Res.  1999,  32:  711 
    CrossrefGoogle Scholar
  • 15 For a review, see: Gnad F. Reiser O. Chem. Rev.  2003,  103:  1603 
    CrossrefPubMedGoogle Scholar
10

Typical Procedure. To a solution of trans-2-(tributylstannyl)-N,N-dibenzyl-cyclopropylamine (3, 526 mg, 1 mmol) in THF (3 mL) was added n-BuLi (1.2 mmol, 2 M in hexane) at -30 °C. After stirring the mixture at -30 °C for 30 min, the respective electrophile (1.2 mmol) was added. The mixture was warmed up to 0 °C within 2 h. At this stage, the reaction was quenched with H2O (10 mL), the mixture extracted with Et2O (3 × 20 mL), dried over MgSO4 and concentrated. The crude product was purified by flash chromatography on silica gel.

11

Spectroscopic data for representative compounds 5d, 5f and 5g:
trans-N-(2-allylcyclopropyl)-N,N-dibenzylamine (5d): IR (KBr): 1640, 1493, 1453, 748, 698 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.21 (ddd, J = 6.7, 4.8, 3.5 Hz, 1 H), 0.46 (ddd, J = 8.6, 4.8, 4.0 Hz, 1 H), 0.61-0.68 (m, 1 H), 1.53 (ddd, J = 6.7, 4.0, 3.1 Hz, 1 H), 1.62-1.70 (m, 1 H), 1.76-1.86 (m, 1 H), 3.48-3.53 (d, J = 13.4 Hz, 2 H), 3.55-3.61 (d, J = 13.4 Hz, 2 H), 4.77-4.90 (m, 2 H), 5.61 (ddt, J = 17.2, 10.1, 6.6 Hz, 1 H), 7.09-7.30 (m, 10 H). 13C NMR (63 MHz, CDCl3): δ = 14.1, 21.1, 36.4, 43.3, 58.3, 114.7, 126.8, 128.0, 129.4, 137.4, 138.8. HRMS (ESI): m/z calcd for C20H24N: 278.1909 [M + H]+; found: 278.1909.
trans-[2-(N,N-dibenzylamino)cyclopropyl] methyl sulfide (5f): IR (KBr): 1494, 1453, 750, 698 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.65 (dt, J = 7.0, 5.1 Hz, 1 H), 0.81 (ddd, J = 8.4, 5.1, 4.3 Hz, 1 H), 1.80 (ddd, J = 8.4, 5.1, 2.6 Hz, 1 H), 1.86 (s, 3 H), 1.93 (ddd, J = 7.0, 4.3, 2.6 Hz, 1 H), 3.58 (s, 4 H), 7.08& ndash;7.28 (m, 10 H). 13C NMR (63 MHz, CDCl3): δ = 16.0, 17.4, 24.0, 47.1, 58.0, 126.9, 128.1, 129.2, 138.3. HRMS (ESI): m/z calcd for C18H22NS: 284.1473 [M + H]+; found: 284.1467.
trans-[2-(N,N-dibenzylamino)cyclopropyl]methanol (5g): IR (KBr): 3354, 1494, 1453, 1028, 749, 698 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.32 (ddd, J = 7.1, 5.3, 5.1 Hz, 1 H), 0.53 (ddd, J = 9.0, 5.1, 3.9 Hz, 1 H), 0.82-0.97 (m, 1 H), 1.15 (br s, 1 H), 1.63 (ddd, J = 7.1, 3.9, 3.2 Hz, 1 H), 3.05 (dd, J = 11.2, 7.9 Hz, 1 H), 3.27 (dd, J = 11.2, 6.4 Hz, 1 H), 3.50 (d, J = 13.4 Hz, 2 H), 3.68 (d, J = 13.4 Hz, 2 H), 7.12-7.30 (m, 10 H). 13C NMR (63 MHz, CDCl3): δ = 11.9, 25.0, 42.8, 59.3, 65.4, 125.4, 128.5, 129.7, 139.1. HRMS (ESI): m/z calcd for C18H22NO: 268.1701 [M + H]+; found: 268.1695.